Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes

Sci Rep. 2015 Aug 19:5:13107. doi: 10.1038/srep13107.

Abstract

Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Gene Expression Regulation*
  • Histone Code / genetics
  • Humans
  • Immunity / genetics*
  • Middle Aged
  • Transcription, Genetic*
  • Young Adult